Acute and chronic smoking reduces peripheral blood flow and shear stress, contributing to the increased incidence of peripheral arterial disease in smokers. Currently, it is not known whether physical activity status influences peripheral blood flow among chronic smokers. Blood flow was measured using Doppler ultrasound on the common femoral artery in nine young otherwise healthy sedentary smokers (eight males/one female) and nine physically-active smokers (six males/three females). Physically-active smokers performed strenuous exercise 4.4 times/week for 8 h/week. No significant differences in body fat, blood pressure, and total cholesterol were observed between groups. Basal femoral artery blood flow was approximately 50% higher in physically-active smokers compared with sedentary smokers (259+/-108 ml min(-1) versus 173+/-47 ml min(-1), P<0.05). The higher basal femoral artery blood flow in physically-active smokers compared with sedentary smokers was associated with a 47% higher femoral artery vascular conductance (2.99+/-1.2 U versus 2.03+/-0.5 U, P<0.05) and a 39% lower vascular resistance (0.38+/-0.13 U versus 0.53+/-0.15 U, P<0.05). Cardiac output, systemic vascular resistance, femoral intima-media thickness, and plasma norepinephrine concentration were not different between the groups. We concluded that smokers who habitually perform physical activity demonstrate greater levels of peripheral blood flow and peripheral vascular conductance. The findings from the present cross-sectional study suggest that chronic smokers may be able to negate, at least in part, the adverse effects of chronic smoking on the peripheral vasculature by performing regular physical activity.